The purpose of the proposed study is to characterize the course of the cellular immune response to herpes simplex virus (HSV) during primary and recurrent infections in man and to identify differences in response between those with severe recurrent and those with nonrecurrent disease. Forty patients with primary herpes progenitalis will have sequential virologic, serologic and cellular immune studies during their first episode and during selected recurrences or at prescribed intervals over the next 18 months. Twenty patients with established recurrent herpes progenitalis will have episodes studied by the same methods for comparison with two groups of controls: 10 seronegative patients with no history of herpetic lesions and 10 seropositive patients with negative histories. Adults with herpes simplex lesions extending beyond a primary site and complicating renal transplantation, lymphoma, leukemia, immunosuppressive chemotherapy or burns, will be studied in a similar manner during the intial and recurrent episodes for 12 months. The virologic studies will include sequential quantitative viral culture, lesional interferon titration, and typing of isolates. Serologic studies will include complement fixation titer for HSV, micro-neutralization titer for HSV 1 and 2, blocking or enhancing activity of serum in an assay of direct lymphocyte-mediated cytotoxicity against HSV-infected cells, and cytolytic antibody titer in antibody-dependent cellular cytotoxicity tests with HSV-infected cells. The tests of cellular immunity utilizing subjects' lymphocytes and monocytes will include HLA typing, lymphocyte proliferative responses to concanavalin A and HSV antigens, lymphocyte interferon production in response to concanavalin A and HSV antigens, a direct lymphocyte-mediated cytotoxicity assay against infected cells and an antibody-dependent cellular cytotoxicity assay. In addition 9 clinical parameters will be recorded during each episode studied.